The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with exposure to pesticides and other agricultural exposures. The study is a collaboration of the National Cancer Institute, the National Institute of Environmental Health Sciences, and the US Environmental Protection Agency. Farmers and their spouses and children are exposed to numerous potential hazards - many of which, such as pesticides, are relevant to the population at large. Farmers have been shown to be at increased risk for some cancers. Experimental and human studies of acute or high-dose exposures suggest that farmers may also be at increased risk of other adverse health effects. We are examining cancer incidence and other health endpoints in a prospective study of licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Over a 3-year period, we enrolled more than 57,000 licensed applicators, representing 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators also completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of farmer applicators enrolled and 2/3 of these also provided data on reproductive health, including information on all children under age 21. Cancer incidence among the applicators, spouses, and children is determined through linkage with the population-based cancer registries in IA and NC. Follow-up computer-assisted telephone interviews are used to update exposure information and to collect information on changes in health status since enrollment in the study. Buccal-cell samples are being collected from participants in order to extract DNA for future analyses of gene and environment interactions. In addition, a dietary assessment (food frequency questionnaire) is self-completed and returned by mail. In-depth assessment of agricultural exposures is being made for a small sample of farmers and their families in order to validate the questionnaires and facilitate exposure classification. Both environmental and biological samples are being collected. Non-cancer outcomes of particular interest in this follow-up period include Parkinson's Disease, autoimmune diseases, and premature ovarian failure in addition to cancer. Planning for the next follow-up phase is underway. Respiratory disease will be a new focus to follow-up on findings vased on cross-sectional enrollment data linking pesticides and other farm exposures to risk for asthma symptoms and and chronic lung diseases. Recent results from the Agricultural Health Study include assessment of cancer incidence after approximately 5 years of follow-up and continued evaluation of potential links between farm exposures and health endpoints. We completed the first round of follow-up interviews and plans are underway for Phase III telephone interviews. Selected results: The overall cancer incidence and mortality among private pesticide applicators and their spouses is lower than expected based on cancer and death rates in the two participating states. A prostate cancer excess was explored in greater detail using follow-up data through 1999. Use of chlorinated pesticides among applicators over age 50 and the use of methyl bromide were significantly associated with prostate cancer risk. A number of pesticides were associated with prostate cancer among applicators with a family history of prostate cancer whereas the same chemicals were not associated with prostate cancer among those without a family prostate cancer history. Lung cancer risk was also shwon to be associated with use of some specific pesticides. In additional analyses of subcohorts using certain pesticides, lung cancer findings were confirmed as were suggestive links between some pesticides and other cancers including multiiple myeloma, rectal cancer, and leukemia. See reports from the National Cancer Institute and teh Agricultural Health Study Website - www.aghealth.org - for further details. We also found that parent's use of pesticides was associated with risk of cancer in their children. The overall risk of cancer before age 20 was slightly increased for children of Iowa farm applicators (SIR 1.4 (95% CI 1.0-1.8) compared to state rates, as was risk of Hodgkin's lymphoma (SIR 2.6, 95% CI 1.1-6.1). Risk could not be linked to specific pesticides although there was suggestive evidence of increased risk associated with father's use of aldrin prior to conception and with poor pesticide hygiene among fathers. We explored risk factors for wheeze, a cardinal symptom of asthma. Wheeze in the past 12 months was associated with raising animals requiring direct contact. Wheeze was associated with the number of poultry and the number of livestock on the farm, as well as with performing tasks that increased direct animal contact. Risks were moderated by smoking and history of atopy. We also found that wheeze was associated with a wide variety of other farm activities, notably those that result in exposure to diesel exhaust and solvents. SImilar result link pesticide exposure to several chronic respiratory diseases. We are also exploring several reproductive health outcomes potentially associated with agricultural exposures. For example,in a submitted manuscript, we show that parental use of solvents appears to be associated with self-reported infertility. While use of pesticides in general did not appear to be associated with age at menopause, some specific chemicals were associated with early age at menopause. We found links between non-agricultural exposures and specific menstrual cycle characteristics which could be indicative of hormone disruption. A preliminary analysis suggests that endocrine disrupting pestsicides affect the cycle characteristics.